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      Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma

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          Abstract

          31P magnetic resonance spectroscopy ( 31P MRS) can measure intracellular pH (pH i) using the chemical shift difference between pH‐dependent inorganic phosphate (P i) and a pH‐independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non‐Hodgkin's lymphoma (NHL). Well‐resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct P i–PCr method was best for those spectra with a very well‐defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the P i–αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water‐based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the P i–αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment‐related changes of the order of 0.1 pH units should be detectable. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

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          Determination of intracellular pH by 31P magnetic resonance.

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            Metabolic recovery after exercise and the assessment of mitochondrial function in vivo in human skeletal muscle by means of 31P NMR.

            It has been suggested that the rate of phosphocreatine resynthesis after exercise is an index of mitochondrial oxidative metabolism in intact muscle. To investigate this hypothesis, the time courses of metabolite recovery following mild and more severe dynamic exercise of human forearm muscle were compared by means of 31P NMR. Severe exercise resulted in greater net hydrolysis of phosphocreatine and greater intracellular acidosis than light exercise. The rate of phosphocreatine resynthesis was significantly slower during recovery from the more severe exercise. To explain this it was noted that, as a consequence of the high activity of creatine kinase in the sarcoplasm, the [phosphocreatine] at any time is a function of the intracellular pH. Calculations demonstrate that the difference between rates of phosphocreatine recovery after the two exercise protocols was primarily determined by the rates of recovery of the intracellular pH to normal rest values. It is concluded that the calculated rate of recovery of the cytosolic free [ADP] to its pre-exercise concentration may provide a more specific measure of mitochondrial oxidative activity.
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              Measurement of human skeletal muscle oxidative capacity by 31P-MR spectroscopy: a cross-validation with in vitro measurements.

              To cross-validate skeletal muscle oxidative capacity measured by (31)P-MR spectroscopy with in vitro measurements of oxidative capacity in mitochondria isolated from muscle biopsies of the same muscle group in 18 healthy adults. Oxidative capacity in vivo was determined from PCr recovery kinetics following a 30-s maximal isometric knee extension. State 3 respiration was measured in isolated mitochondria using high-resolution respirometry. A second cohort of 10 individuals underwent two (31)P-MRS testing sessions to assess the test-retest reproducibility of the method. Overall, the in vivo and in vitro methods were well-correlated (r = 0.66-0.72) and showed good agreement by Bland Altman plots. Excellent reproducibility was observed for the PCr recovery rate constant (CV = 4.6%; ICC = 0.85) and calculated oxidative capacity (CV = 3.4%; ICC = 0.83). These results indicate that (31)P-MRS corresponds well with gold-standard in vitro measurements and is highly reproducible. Copyright © 2011 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                NMR Biomed
                NMR Biomed
                10.1002/(ISSN)1099-1492
                NBM
                Nmr in Biomedicine
                John Wiley and Sons Inc. (Hoboken )
                0952-3480
                1099-1492
                04 November 2013
                February 2014
                : 27
                : 2 ( doiID: 10.1002/nbm.v27.2 )
                : 158-162
                Affiliations
                [ 1 ] Cancer Research‐UK and EPSRC Cancer Imaging Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust Division of Radiotherapy and Imaging/MRI Unit, Downs Road, Sutton, Surrey, SM2 5PT United Kingdom
                Author notes
                [*] [* ] Correspondence to: Prof. M. O. Leach, Cancer Research‐UK and EPSRC Cancer Imaging Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Division of Radiotherapy and Imaging/MRI Unit, Downs Road, Sutton, Surrey, SM2 5PT, United Kingdom.

                E‐mail: Martin.Leach@ 123456icr.ac.uk

                Article
                NBM3047 NBM-13-0145.R1
                10.1002/nbm.3047
                4290015
                24738141
                3eaa09ba-9de9-45c0-bcab-0ee66a2f5479
                © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 July 2013
                : 02 October 2013
                : 03 October 2013
                Page count
                Pages: 5
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                nbm3047
                February 2014
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.6 mode:remove_FC converted:01.03.2016

                Radiology & Imaging
                31p mrs,intracellular ph,non‐hodgkin's lymphoma,reference peak,accuracy measurement,java‐based magnetic resonance user interface (jmrui)

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